DESCRIPTION: (Applicant's Description): There are emerging data to suggest that fetal, early childhood and adolescent exposures related to growth, nutrition and physical activity may be associated with risk of breast cancer. In addition, although there are strong and consistent data that mammographic breast density is related to subsequent risk of breast cancer, little is known about the natural history and predictors of this major risk factor. We propose to evaluate these questions in the Breast Cancer Family Study, an ongoing study in families of 426 women with breast cancer who were ascertained in the years 1944-1952. From 1991-1996, we updated the pedigrees to include 11,848 women, of whom 7,456 were alive; we also collected detailed information on recognized breast cancer risk factors through a telephone interview of 6,194 women who were at least age 18 and medically able to be interviewed (93 percent response rate). In this project, we propose to conduct an epidemiologic follow-up of the women who participated in this interview. Specifically, we plan to: 1) conduct two risk factor surveys by mailed questionnaire among these cohort members (Years 1 & 4) to update risk factor information, collect new data on early life exposures, update mammography use, and to ascertain new cases of breast and other cancers; and; 2) obtain serial mammographic films on all women who are age- and medically-eligible for mammography. This will allow us to examine the association of early life factors with breast cancer risk, and the interaction of these factors with family history of breast cancer. We will also describe the rate of change in mammographic percent density, and examine the association of breast cancer risk factors (including early life factors) with change in mammographic density over a period of up to 10 years. Finally, we will conduct exploratory analyses to examine the association of percent breast density and other novel aspects of mammogram with breast cancer risk using a nested-case control design. These data will provide new insights into the role of selected factors in breast cancer risk, including information from a period of life that is increasingly recognized as playing an important role in breast cancer etiology, and will provide further insight into the natural history and role of breast density in this disease. Such data would be expected to better inform the primary prevention of breast cancer.